16-27600340-T-C

Variant names:

• chr16-27600340-T-C
• rs10492922
• NM_015202.5:c.64-18085T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015202.5(KATNIP):​c.64-18085T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,228 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.079 (579 hom., cov: 32)
• Consequence: KATNIP NM_015202.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 4 publications found

Genes affected

KATNIP (HGNC:29068): (katanin interacting protein) This gene encodes a novel, evolutionarily conserved, ciliary protein. In human hTERT-RPE1 cells, the protein is found at the base of cilia, decorating the ciliary axoneme, and enriched at the ciliary tip. The protein binds to microtubules in vitro and regulates their stability when it is overexpressed. A null mutation in this gene has been associated with Joubert syndrome, a recessive disorder that is characterized by a distinctive mid-hindbrain and cerebellar malformation and is also often associated with wider ciliopathy symptoms. Consistently, in a serum-starvation ciliogenesis assay, human fibroblast cells derived from patients with the mutation display a reduced number of ciliated cells with abnormally long cilia. [provided by RefSeq, Feb 2016]

KATNIP Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Joubert syndrome 26

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015202.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNIP	NM_015202.5	MANE Select	c.64-18085T>C		intron	N/A	NP_056017.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNIP	ENST00000261588.10	TSL:1 MANE Select	c.64-18085T>C		intron	N/A	ENSP00000261588.4
	KATNIP	ENST00000568258.5	TSL:3	c.49-18085T>C		intron	N/A	ENSP00000454884.1
	KATNIP	ENST00000565672.5	TSL:3	n.33+26384T>C		intron	N/A	ENSP00000455380.1

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11971 AN: 152110 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.0641

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0787 AC: 11982 AN: 152228 Hom.: 579 Cov.: 32 AF XY: 0.0827 AC XY: 6153 AN XY: 74436

African (AFR) AF: 0.0919 AC: 3818 AN: 41530

American (AMR) AF: 0.0509 AC: 779 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00642 AC: 31 AN: 4830

European-Finnish (FIN) AF: 0.171 AC: 1811 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5273 AN: 68004

Other (OTH) AF: 0.0634 AC: 134 AN: 2114

Alfa AF: 0.0695 Hom.: 757

Bravo AF: 0.0699

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.63
PhyloP100		0.053
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10492922; hg19: chr16-27611661;